Effective Technique Using Combined CO2 Laser and Pulsed Dye Laser for Facial Angiofibromas Management in Tuberous Sclerosis

Background Facial angiofibromas (FAs) are a dermatological characteristic which are typically linked to tuberous sclerosis (TS). Aim We discuss our experience, highlighting a rare occurrence of multiple FAs in a young patient, successfully treated with ablative CO2 laser combined with PDL therapy. Methods A 23-year-old male patient affected by TS who presents multiple erythematous and colored papules/nodules located on the face, mainly concentrated around nose, perinasal area, cheeks, and chin area, was treated with a combination of ablative CO2 laser and a pulsed dye laser. The patient underwent 3 sessions of combined treatment with CO2 and pulsed dye laser. The intralesional dye laser treatment was administered immediately after the CO2 laser session. The time interval between the combined laser treatments was approximately two months. Results After 4 months from the last laser treatment session, most of the facial erythematous and protruding lesions had improved. Following these procedures, the patient did not experience complications or severe adverse reaction. Conclusion The combined use of the CO2 and dye laser has been proved to be a safe and effective treatment for multiple FAs in the young patient affected by tuberous sclerosis.


Introduction
Facial angiofbromas (FAs) are a dermatological characteristic which are typically linked to tuberous sclerosis (TS).FAs can have a prevalence of up to 90% [1] and frequently lead patients to contact with specialists about cosmetic procedures to improve their appearance [2].
Te use of mTOR inhibitors like sirolimus (rapamycin) has signifcantly improved the treatment of TS cutaneous symptoms [14,15].However, topical sirolimus rarely results in complete treatment of angiofbromas.Indeed, the adult patients with fully grown angiofbromas respond less favourably to topical rapamycin treatment as demonstrated by Park et al. [8] who showed that the application of topical rapamycin was inefective in the treatment of papules larger than 4 mm.In this instance, the large FAs can be efectively treated with rapamycin combined to laser therapy [16].
On the other hand, the cryotherapy or shave excision followed by dermabrasion is a simple procedure to use, but it presents various drawbacks, such as postoperative discomfort and hypopigmented scarring in susceptible patients [17].
As a result, physical treatment to diminish the size of both old and advanced lesions, especially for individuals who did not receive early care or who have had the condition for a long time, has been widely employed.
Laser therapy is considered an efective treatment for angiofbromas [18].
Te existing literature already reported clinical cases in which the ablative and nonablative laser combination technique has led to good results in the resolution of TSrelated angiofbroma lesions [19].Especially, the combination of PDL and CO 2 laser was successfully used for vascular lesions management [20,21].
Herein, we discuss our experience, highlighting a rare occurrence of multiple FAs in young patient, successfully treated with ablative CO 2 laser combined with PDL therapy.

Case Presentation
We report a clinical case of a 23-year-old male patient affected by tuberous sclerosis (TS) who manifests neurological symptoms represented by a mild mental retardation.Patient presents multiple erythematous and colored papules/nodules and raised erythematous elevated plaque located on the face, mainly concentrated around nose, perinasal area, cheeks, and chin area.Te multiple papules measured up to 0.5 cm in size.Te onset of TS symptoms occurred in adolescents, immediately prior to puberty.TS was confrmed by brain magnetic resonance imaging.Prior to the study, the patient did not receive any pharmaceutical therapies.
Since redness and volume of the lesions were the main cause of patient's cosmetic problems, a combinational laser therapy, including the use of the ablative CO 2 laser (Tet-raPro-DEKA M.E.L.A, Calenzano, Italy) and a pulsed dye laser (Synchro VasQ-DEKA M.E.L.A, Calenzano, Italy), was administered.
Te patient underwent 3 sessions of combined treatment with CO 2 and pulsed dye laser.
Te intralesional dye laser treatment was administered immediately after the CO 2 laser session.Te time interval between the combined laser treatments was approximately two months.A topic occlusive anaesthetic mask was applied 20 minutes before treatment with CO 2 laser.
For CO 2 laser therapy, parameters were set to frequency 10 Hz, power 0.4-1.5 W, SP pulse.PDL was performed immediately after CO 2 laser, and parameters of spot size 10-12 mm and fuence 7 J/cm 2 were selected.A clinical photography-based assessment of the Facial Angiofbromata Severity Index (FASI) was used to determine the efectiveness of the treatment at the baseline and four months following the fnal laser treatment session.Te FASI scores range from 0 (the best) to 3 (the worst), encompassing erythema (0-3), size (0-3), and extent (0, 2, or 3).In addition, the Dermatology Life Quality Index (DLQI) before and four months following the fnal laser treatment session was administered to the patient in order to assess the patient's level of satisfaction.Te fnal DLQI score ranges from 0 (no impact on quality of life) to 30 (maximum impairment).Following combined laser therapy, most of the facial angiofbromas have shown remarkable improvement in redness and size.After 4 months from the last laser treatment session, most of the facial erythematous and protruding lesions had improved, as clearly shown in Figure 1.Te PDL laser treatment interval was extended to a monthly frequency of 6 months as a maintenance therapy to avoid the reappearance of angiofbromas.Following these procedures, the patient did not experience complications or severe adverse reaction.Intense purpura on the face was observed immediately after the dye laser procedure (Figure 2), but these conditions considerably disappeared after a week.
FASI indicates that all variables (redness, size, and extension) in our clinical image were considerably improved.Te FASI score decreased from 9 at the baseline to 0 at four months of follow-up from the last laser treatment session.DLQI scores varied from 25 at the baseline to 2 at four months follow-up from the last laser treatment session indicating a marked impairment on patient's quality of life following the laser therapy.
At postoperative therapy, healing creams based on hyaluronic acid and an antibiotic cream were applied to the patient's face after careful cleaning of the wounds with gauze and saline solution.During and after the research study period, patients were also instructed to limit further photodamage by using sunscreen with a 50-sun protection factor.
In conjunction with maintenance treatment with dye laser, the use of topical rapamycin can be recommended to the patient in order to avoid the return of the vascular symptoms of angiofbromas.

Discussion
A laser combination therapy may be required for patients afected by angiofbromas [9].Multiple laser treatment has been shown to reduce the risk of dyspigmentation and scarring while maximizing the therapeutic efcacy of each modality [13].Among these, the combination of PDL laser and the CO 2 laser was successfully tested [2].
PDL by targeting the vascular components of the FAs lesions, it is able to improve erythema in more than 90% of patients with predominant vascular components but without decreasing the fbrous component [9].For this purpose, the ablative CO 2 laser therapy has been used for its efectiveness in reducing the size of the fbrous component compared with PDL.Indeed, elevated lesions have been fattened using the CO 2 laser since it is the best option for accurate, safe ablation with good hemostasis; by creating a matrix-shaped microthermal damage, fractional CO 2 lasers stimulate the basic repair process in the dermis and in the epidermis, leading to skin regeneration and repairing.
Te present case report confrms the efectiveness of this combined laser technique where the global improvement of the functional and aesthetic patient-reported outcomes was done by the CO 2 healing process through excision and tissue regeneration and the action of the nonablative 595 nm laser, which provides more control over the healing process.
Our fndings showed a great improvement of patient's skin lesions, and the results were evident immediately after the frst treatment.All erythematous and prominent papules have exhibited notable improvements in size and redness at four months after the last laser therapy session as documented by clinical images and FASI results.
According to DLQI scores, the results achieved after treatment at the follow-up revealed that the condition has 2 Case Reports in Dermatological Medicine completely lost its negative impact on the daily lives of the patient.Furthermore, the patient did not experience complications or recurrence.Usually, the rapamycin may have had an additive efect in lesion regression and maintenance due to its antiangiogenic activity and by blocking proliferation of abnormal fbroblasts [22].However, prospective research including 25 TS patients showed that topical rapamycin cream maintenance treatment administered three times a week was inefective in preventing TSC recurrence [23].Consequently, in our study, as a primary choice, we favoured the use of dye laser as a maintenance therapy to avoid the reappearance of FAs.However, under medical evaluation, in conjunction with maintenance treatment with dye laser, the topical rapamycin can be administered.
In contrast in the study of Neamonitou et al. [24], patients who manifest recurrence were retreated with CO 2 laser.Tis research was not in line with our study protocol as the subjects received a triple laser therapy (CO 2 laser, erbium laser, and PDL) in one session, achieving good results.However, the CO 2 laser employed in our research ofers an innovative technology which permits users to simulate the Er-YAG laser efect by modulating the power and pulse parameters.In this way, we can reduce the coagulative efect in order to obtain a superfcial skin resurfacing and a reduction of skin lesion thickness.It represents a noninvasive Case Reports in Dermatological Medicine and not painful technology that did not require the use of anaesthesia, which is instead used in other studies [24,25]; this makes the system also suitable to treat individuals who exhibit neurological signs, such as our clinical case.
A multiple combined session of diferent lasers was also used in the study of Fioramonti et al. [17] where all patients showed great improvement of their skin lesions with no complications or recurrence.
Te absence of skin biopsy specimen examination of the face papules and a longer follow-up period in order to monitor the recurrence rate were the primary study limitations.In conclusion, the combined use of the CO 2 and dye laser has been proved to be a safe and efective treatment for multiple FAs in the young patient afected by tuberous sclerosis.

Figure 1 :
Figure 1: (a, b) Right and left lateral views of FAs located on the face of the young male patient.(c, d) Right and left lateral views of the same male patient at 4 months of follow-up after the last laser treatment session.A marked improvement of skin lesions was observed in all treated area.